Therapeutic potential for P2Y 2 receptor antagonism.

Autor: Jasmer KJ; Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO, USA.; Department of Biochemistry, University of Missouri, Columbia, MO, USA., Muñoz Forti K; Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO, USA.; Department of Biochemistry, University of Missouri, Columbia, MO, USA., Woods LT; Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO, USA.; Department of Biochemistry, University of Missouri, Columbia, MO, USA., Cha S; Department of Oral and Maxillofacial Diagnostic Sciences, Center for Orphaned Autoimmune Disorders, University of Florida College of Dentistry, Gainesville, FL, USA., Weisman GA; Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO, USA. weismang@missouri.edu.; Department of Biochemistry, University of Missouri, Columbia, MO, USA. weismang@missouri.edu.
Jazyk: angličtina
Zdroj: Purinergic signalling [Purinergic Signal] 2023 Jun; Vol. 19 (2), pp. 401-420. Date of Electronic Publication: 2022 Oct 11.
DOI: 10.1007/s11302-022-09900-3
Abstrakt: G protein-coupled receptors are the target of more than 30% of all FDA-approved drug therapies. Though the purinergic P2 receptors have been an attractive target for therapeutic intervention with successes such as the P2Y 12 receptor antagonist, clopidogrel, P2Y 2 receptor (P2Y 2 R) antagonism remains relatively unexplored as a therapeutic strategy. Due to a lack of selective antagonists to modify P2Y 2 R activity, studies using primarily genetic manipulation have revealed roles for P2Y 2 R in a multitude of diseases. These include inflammatory and autoimmune diseases, fibrotic diseases, renal diseases, cancer, and pathogenic infections. With the advent of AR-C118925, a selective and potent P2Y 2 R antagonist that became commercially available only a few years ago, new opportunities exist to gain a more robust understanding of P2Y 2 R function and assess therapeutic effects of P2Y 2 R antagonism. This review discusses the characteristics of P2Y 2 R that make it unique among P2 receptors, namely its involvement in five distinct signaling pathways including canonical Gα q protein signaling. We also discuss the effects of other P2Y 2 R antagonists and the pivotal development of AR-C118925. The remainder of this review concerns the mounting evidence implicating P2Y 2 Rs in disease pathogenesis, focusing on those studies that have evaluated AR-C118925 in pre-clinical disease models.
(© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)
Databáze: MEDLINE
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